Improved powderous formulations of organic acid amides having an aromatic ring system

ABSTRACT

The present invention relates to improved powderous formulations comprising organic acid amides having an aromatic ring system as well as to the production of such formulations.

The present invention relates to improved powderous formulationscomprising organic acid amides having an aromatic ring system as well asto the production of such formulations.

Powderous formulations of organic acid amides having an aromatic ringsystem are very common and useful formulations. They can then beincorporated in any kind of product wherein such an acid amide isneeded.

An example of such an organic acid amide is nicotinamide.

Nicotinamide, which is the amide of nicotinic acid (also known asvitamin B3, niacin and vitamin PP) is an essential human nutrient.

When these organic acid amides are used in a powder form, theseformulations do unfortunately have a tendency to explode.

Even when the powder has a prominent amount of larger particles, thereis always a certain amount of small particles present. These smallparticles are responsible for the explosion risk.

Dust explosions are a huge risk in any processes wherein powders areused. Therefore there is a need for powderous formulations with lowexplosion hazard. But nevertheless the powderous formulations must stillhave the essential (and advantageous) features of a powder, such as freeflowable, easy to transport, easy to dosage etc.

It is known from the prior art that certain auxiliary compounds andcarrier material, can minimize the explosion risk of powderousformulation comprising vitamin E.

Due to the importance of such non-explosive formulations, there isalways a need for improved formulation.

Surprisingly, it was found out that formulations with a very high activeingredient content of 65 weight-% (wt-%) and more, based on the totalweight of the powderous formulation can be provided. Furthermore thereis no need for a carrier material.

It was found that powderous formulations comprising

65-95 wt-%, based on the total weight of the powderous formulation, ofat least one compound of formula (I)

wherein

X is —N— or —CH— and

R¹ is H or a C₁-C₄ alkyl moiety, andR² is H or a C₁-C₄ alkyl moiety, andcomprising one or more specific compounds (auxiliary compound), do havea low risk of explosion.

Therefore the present application relates to powderous formulations (I)comprising

-   -   (i) 65-95 wt-%, based on the total weight of the powderous        formulation, of at least one compound of formula (I)

-   -   wherein    -   X is —N— or —CH— and    -   R¹ is H or a C₁-C₄ alkyl moiety, and    -   R² is H or a C₁-C₄ alkyl moiety, and    -   (ii) 5-35 wt-%, based on the total weight of the powderous        formulation, of at least one auxiliary compound selected from        the group consisting of aluminum ammonium sulphate, aluminum        potassium sulfate, ammonium acetate, ammonium bisulphite,        ammonium carbonate, ammonium chloride, ammonium dihydrogen        phosphate, ammonium hydrogen carbonate, bentonite,        montmorillonite, calcium aluminates, calcium carbonate, calcium        silicate, synthetic calcium sulphate dihydrate, calcium sulfate,        kaolinitic clays (such as Kaolin), diatomaceous earth, perlite,        potassium bisulphite, potassium hydrogen carbonate, potassium        sulphate, potassium carbonate, sepiolitic clays, silicic acid,        synthetic sodium aluminosilicate, sodium aluminosulfate, sodium        bisulphate, sodium carbonate, sodium chloride, sodium hydrogen        carbonate, sodium sulphate, vermiculite, calcium carbonate,        magnesium carbonate, calcareous marine algae, magnesium oxide,        magnesium sulphate, dicalcium phosphate, tri-calcium phosphate,        mono-dicalcium phosphate, defluorinated rock-phosphate,        monocalcium phosphate, calcium-magnesium phosphate,        mono-ammonium phosphate, magnesium phosphate,        sodium-calciummagnesium phosphate, mono-sodium phosphate,        glycerol, propylene glycol (E 1520), glyceryl triacetate        (E1518), sorbitol (E420), polydextrose, lactic acid and urea.

Preferably, R¹ in the definition of formula (I) is H, CH₃, CH₂CH₃,(CH₂)₂CH₃ and (CH₂)₃CH₃. More preferably R¹ is H or CH₃.

Preferably, R² in the definition of formula (I) is H, CH₃, CH₂CH₃,(CH₂)₂CH₃ and (CH₂)₃CH₃. More preferably R² is H or CH₃.

Preferably X is N.

Therefore the present invention relates to a powderous formulation (I′),which is formulation (I) wherein R¹ in the definition of formula (I) isH, CH₃, CH₂CH₃, (CH₂)₂CH₃ and (CH₂) CH₃ (preferably H or CH₃) andwherein R² in the definition of formula (I) is H, CH₃, CH₂CH₃, (CH₂)₂CH₃and (CH₂)₃CH₃ (preferably H or CH₃) and wherein X in the definition offormula (I) is N.

It is clear that the sum of all the wt-%'s always add up to 100.

In the context of the present invention the specific compounds (ii) arealso defined as auxiliary compounds.

Compounds of formula (Ia) are preferred

Therefore the present invention relates to a powderous formulation (II),which is formulation (I) or (I′), wherein at least one compound offormula (Ia) is used.

More preferred is the compound of formula (Ia),

which is nicotinamide.

Therefore the present invention relates to a powderous formulation(III), which is formulation (I), (I′) or (II), wherein the compound offormula (Ia′) is used.

Preferably, the auxiliary compounds have an average particle size (d0.5) (in the powderous formulation) of 10 μm-100 μm.

Furthermore preferred are formulations (IV), which are formulations (I),(I′), (II) or (III), wherein the auxiliary compound has an averageparticle size (d 0.5) of 10 μm-100 μm.

The average particle sizes are measured by a Malvern Master Sizer 2000.During this laser diffraction measurement, particles are passed througha focused laser beam. These particles scatter light at an angle that isinversely proportional to their size. The angular intensity of thescattered light is then measured by a series of photosensitivedetectors. The map of scattering intensity versus angle is the primarysource of information used to calculate the particle size. For themeasurement of dry materials such as the applied additives, a dry powderfeeder (Malvern Scirocco) was used.

The explosion hazard of powders (dusts) is usually measured by astandardized method (EN 13821:2002 (Determination of minimum ignitionenergy of dust/air mixtures)). This is the method which is used for thedetermination of all MIE values in this patent application. This methodallows to determining the minimum ignition energy (MIE) of a powder. TheMIE is the minimum amount of energy required to ignite a combustiblevapor, gas or dust cloud, for example due to an electrostatic discharge.MIE is measured in joules (J).

The average size of the powder particles for the measurement accordingto the procedure in EN 13821:2002 is ≦63 μm.

All the MIE values in this patent application are determined by using amodified Hartmann tube (type MIKE 3) available from Adolf Kühner AG(Birsfelden, CH). This equipment is specially designed to allow themeasurement of very low ignition energies. This is achieved by havingdifferent capacitors installed. The capacitors are designed to store theenergy of 1 mJ, 3 mJ, 10 mJ, 30 mJ, 100 mJ, 300 mJ and 1000 mJ.

When measuring the MIE of commercially available powderous formulationscomprising at least one compound of formula (I), they are usually in therange of 1-3 mJ. This means that a very low amount of energy issufficient to initiate an explosion.

On the other hand, the formulations according to the present inventionhave MIE values in the range of 10-100 mJ.

Therefore the present invention relates to formulations (V), which areformulations (I), (I′), (II), (III) or (IV) with MIE values of 10-100 mJ(determined by the method of EN 13821:2002).

The formulations according to the present invention are dry powders. Butdepending on the process of production as well as the storageconditions, the formulations can comprise some water. The water contentis usually below 5 wt-%, based on the total weight of the formulation.

Therefore a further embodiment of the present invention relates toformulations (VI), which are formulations (I), (I′), (II), (III), (IV)or (V), wherein 0-5 wt-%, based on the total weight of the formulation,of water is present.

The compounds of formula (I) can be from a natural source or they can besynthesised. Due to the nature of either the isolation process or theprocess of production, it is possible that traces of side products arepresent.

Optionally a carrier material can be used in the powderous formulationaccording to the present invention.

The optional carrier material used in the formulations according to thepresent invention are commonly known and used carrier material. Asuitable carrier material is synthetically produced precipitated silicaor formiate (such as calcium formiate). This carrier material consistsof porous particles. Other suitable carrier materials are proteins,starches, lignosulfonates and gums.

Preferably the powderous formulations do not comprise otheringredients/compounds than those as disclosed above. They do not containany commonly used stabilisers, carrier material, surface activeingredients or sugars.

Preferred formulations of the present invention are formulations (VII),which are formulations (I), (I′), (II), (III), (IV), (V) or (VI)comprising

-   -   (ii) 5-35 wt-%, (preferably 10-30 wt-%), based on the total        weight of the formulation, of at least one compound selected        from the group consisting of ammonium dihydrogen phosphate,        (purified) diatomaceous earth, potassium hydrogen carbonate,        potassium sulphate, potassium carbonate, sodium chloride and        sodium hydrogen carbonate.

More preferred are formulations (VII′), which are formulations (VII)with MIE values of 10-100 mJ (determined by the method of EN13821:2002).

Furthermore preferred are formulations (VII′), which are formulations(VII′) wherein the auxiliary compound has an average particle size (d0.5) of 10 μm-100 μm.

As disclosed above, an advantage of the present formulation is—besidesthe high amount of the acid amide—that it can consist of one or moreacid amides and one or more auxiliary compound (and eventually somewater).

An especially preferred embodiment of the present invention relates toformulations (VIII), consisting of

-   -   (i) 70-90 wt-%, based on the total weight of the powderous        formulation, of at least one compound of formula (Ia)

-   -   (ii) 10-30 wt-%, based on the total weight of the powderous        formulation, of at least one auxiliary compound selected from        the group consisting of ammonium dihydrogen phosphate,        (purified) diatomaceous earth, potassium hydrogen carbonate,        potassium sulphate, potassium carbonate, sodium chloride, sodium        sulphate and sodium hydrogen carbonate, and        0-5 wt-%, based on the total weight of the powderous        formulation, of water.

A very especially preferred embodiment of the present invention relatesto formulations (IX), consisting of

-   -   (i) 70-90 wt-%, based on the total weight of the powderous        formulation, of

-   -   (ii) 10-30 wt-%, based on the total weight of the powderous        formulation, of sodium chloride, and        0-5 wt-%, based on the total weight of the powderous        formulation, of water.

To produce a powder according to the present invention (formulations(I), (I′), (II), (III), (IV), (IV′), (IV″), (V), (VI), (VII), VII′),(VII″), (VIII) and/or (IX)) the at least one compound of formula (I) isblended with at least one auxiliary compound. This process can becarried out by using any usually used blenders. The sequence of addingthe compounds is not essential for the invention.

All the above disclosed formulations (I), (I′), (II), (III), (IV),(IV′), (IV″), (V), (VI), (VII), VII′), (VII″), (VIII) and/or (IX) can beused as such or in food products, feed products and personal careproducts.

Furthermore, the present invention relates to a process of production offood products, feed products and personal care products using at leastone formulation (I), (I′), (II), (III), (IV), (IV′), (IV″), (V), (VI),(VII), VII′), (VII″), (VIII) and/or (IX).

All the above disclosed formulations (I), (I′), (II), (III), (IV),(IV′), (IV″), (V), (VI), (VII), VII′), (VII″), (VIII) and/or (IX) can beused as such in the production of food products, feed products andpersonal care products.

Furthermore the invention also relates to food products, feed productsand personal care products comprising at least one formulations (I),(I′), (II), (III), (IV), (IV′), (IV″), (V), (VI), (VII), VII′), (VII″),(VIII) and/or (IX).

The invention is illustrated by the following Examples. All temperaturesare given in ° C. and all parts and percentages are related to theweight.

EXAMPLES Example 1

850 g nicotinamide (Rovimix® Nicotinamide from DSM) (purity 99.5%) wasfilled into an appropriate blender (Turbula) and 150 g sodium chloridehaving a particle size, analysed by laser diffraction, of 54 μm wasadded, the mix then blended for 10 minutes. The material was thentransferred to a Retsch Grindomixer and milled (10′000 rpm/1 min.). Themedian size of this material was 31 μm. The obtained white powder wasfilled into a container.

The powder was analysed according to the above mentioned EN 13821:2002and the minimum ignition energy was found to be 10-30 mJ.

Example 2

750 g nicotinamide (Rovimix® Nicotinamide from DSM) (purity 99.5%) wasfilled into an appropriate blender (Turbula) and 250 g sodium chloridehaving a particle size, analysed by laser diffraction, of 54 μm wasadded, the mix then blended for 10 minutes. The material was thentransferred to a Retsch Grindomixer and milled (10′000 rpm/1 min.). Themedian size of this material was 30 μm. The obtained white powder wasfilled into a container.

The powder was analysed according to the above mentioned EN 13821:2002and the minimum ignition energy was found to be 30-100 mJ.

1. A powderous formulations (I) comprising (i) 65-95 wt-% (preferably70-90 wt-%), based on the total weight of the powderous formulation, ofat least one compound of formula (I)

wherein X is —N— or —CH— and R¹ is H or a C₁-C₄ alkyl moiety, and R² isH or a C₁-C₄ alkyl moiety, and (ii) 5-35 wt-% (preferably 10-30 wt-%),based on the total weight of the powderous formulation, of at least oneauxiliary compound selected from the group consisting of aluminumammonium sulphate, aluminum potassium sulfate, ammonium acetate,ammonium bisulphite, ammonium carbonate, ammonium chloride, ammoniumdihydrogen phosphate, ammonium hydrogen carbonate, bentonite,montmorillonite, calcium aluminates, calcium carbonate, calciumsilicate, synthetic calcium sulphate dihydrate, calcium sulfate,kaolinitic clays (such as Kaolin), diatomaceous earth, perlite,potassium bisulphite, potassium hydrogen carbonate, potassium sulphate,potassium carbonate, sepiolitic clays, silicic acid, synthetic sodiumaluminosilicate, sodium aluminosulfate, sodium bisulphate, sodiumcarbonate, sodium chloride, sodium hydrogen carbonate, sodium sulphate,vermiculite, calcium carbonate, magnesium carbonate, calcareous marinealgae, magnesium oxide, magnesium sulphate, dicalcium phosphate,tri-calcium phosphate, mono-dicalcium phosphate, defluorinatedrock-phosphate, monocalcium phosphate, calcium-magnesium phosphate,mono-ammonium phosphate, magnesium phosphate, sodium-calcium-magnesiumphosphate, mono-sodium phosphate, glycerol, propylene glycol (E 1520),glyceryl triacetate (E1518), sorbitol (E420), polydextrose, lactic acidand urea.
 2. Powderous formulations according to claim 1, wherein R¹ inthe definition of formula (I) is H, CH₃, CH₂CH₃, (CH₂)₂CH₃ and(CH₂)₃CH₃, and R² in the definition of formula (I) is H, CH₃, CH₂CH₃,(CH₂)₂CH₃ and (CH₂)₃CH₃, and X is N.
 3. Powderous formulations accordingto claim 1, wherein R₂ is H or CH₃, and R₁ is H or CH_(3.)
 4. Powderousformulations according to claim 1, comprising (i) 65-95 wt-%, based onthe total weight of the powderous formulation, of at least one compoundof formula (Ia)


5. Powderous formulations according to claim 1, comprising (i) 65-95wt-%, based on the total weight of the powderous formulation, of acompound of formula (Ia′)


6. Powderous formulations according to claim 1, wherein the auxiliarycompound has an average particle size (d 0.5) of 10 μm-100 μm. 7.Powderous formulations according to claim 1, having MIE values of 10-100mJ (determined by the method of EN 13821:2002).
 8. Powderousformulations according to claim 1, wherein 0-5 wt-%, based on the totalweight of the formulation, of water is present.
 9. Powderousformulations according to claim 1, optionally comprising a carriermaterial chosen from the group consisting of synthetically producedprecipitated silica or formiate (such as calcium formiate), proteins,starches, lignosulfonates and gums.
 10. Powderous formulations accordingto claim 1, comprising (ii) 5-35 wt-%, (preferably 10-30 wt-%), based onthe total weight of the formulation, of at least one compound selectedfrom the group consisting of ammonium dihydrogen phosphate, (purified)diatomaceous earth, potassium hydrogen carbonate, potassium sulphate,potassium carbonate, sodium chloride and sodium hydrogen carbonate. 11.Powderous formulations according to claim 1, consisting of (i) 70-90wt-%, based on the total weight of the powderous formulation, of

(ii) 10-30 wt-%, based on the total weight of the powderous formulation,of at least one auxiliary compound selected from the group consisting ofammonium dihydrogen phosphate, (purified) diatomaceous earth, potassiumhydrogen carbonate, potassium sulphate, potassium carbonate, sodiumchloride, sodium sulphate and sodium hydrogen carbonate, and 0-5 wt-%,based on the total weight of the powderous formulation, of water. 12.Use of at least one formulation according to claim 1 in food products,feed products and personal care products.
 13. Food products, feedproducts and personal care products comprising at least one formulationaccording to claim 1.